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Author Notes:

Address correspondence to: Richard A. Kahn (rkahn@emory.edu).

We thank a number of colleagues for their gifts of key reagents used in these studies, including Tamara Caspary (Emory University; Arl13b antibody), David Chan (CalTech; mouse embryonic fibroblasts), Gia Voeltz (University of Colorado at Boulder; plasmid directing expression of mCherry-Sec61β), and Juan Carlos Zabala (Universidad de Cantabria; antibodies to cofactors A/B/C/E).

Subject:

Research Funding:

This work was supported by grants from the National Institutes of Health (NIH; Grant no. GM-122568 to R.A.K.; Grant no. GM-120271 to D.R.).

The collection, validation, and distribution of human fibroblasts from LND patients is supported by NIH R56 NS-102980 (H.A.J.).

This research project was supported in part by Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience NINDS Core Facilities Grant no. 5P30NS055077.

The EuroBioImaging Facility at the Institute of Protein Biochemistry is funded by grants from MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca), Government of Italy.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • INOSINE MONOPHOSPHATE DEHYDROGENASE
  • ENDOPLASMIC-RETICULUM
  • CRYSTAL-STRUCTURE
  • COFACTOR-D
  • IMMATURE THYMOCYTES
  • IMP DEHYDROGENASE
  • ARF FAMILY
  • PROTEIN
  • ARL2
  • BINDING

Compositional complexity of rods and rings

Tools:

Journal Title:

Molecular Biology of the Cell

Volume:

Volume 29, Number 19

Publisher:

, Pages 2303-2316

Type of Work:

Article | Final Publisher PDF

Abstract:

Rods and rings (RRs) are large linear- or circular-shaped structures typically described as polymers of IMPDH (inosine monophosphate dehydrogenase). They have been observed across a wide variety of cell types and species and can be induced to form by inhibitors of IMPDH. RRs are thought to play a role in the regulation of de novo guanine nucleotide synthesis; however, the function and regulation of RRs is poorly understood. Here we show that the regulatory GTPase, ARL2, a subset of its binding partners, and several resident proteins at the endoplasmic reticulum (ER) also localize to RRs. We also have identified two new inducers of RR formation: AICAR and glucose deprivation. We demonstrate that RRs can be disassembled if guanine nucleotides can be generated by salvage synthesis regardless of the inducer. Finally, we show that there is an ordered addition of components as RRs mature, with IMPDH first forming aggregates, followed by ARL2, and only later calnexin, a marker of the ER. These findings suggest that RRs are considerably more complex than previously thought and that the function(s) of RRs may include involvement of a regulatory GTPase, its effectors, and potentially contacts with intracellular membranes.

Copyright information:

© 2018 Schiavon et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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